ID   PENA_PENCR              Reviewed;         368 AA.
AC   A0A0E3D8L0;
DT   10-APR-2019, integrated into UniProtKB/Swiss-Prot.
DT   24-JUN-2015, sequence version 1.
DT   25-MAY-2022, entry version 11.
DE   RecName: Full=Terpene cyclase penA {ECO:0000250|UniProtKB:A0A455R4Z0};
DE            EC=5.4.99.- {ECO:0000250|UniProtKB:A0A455R4Z0};
DE   AltName: Full=Penitrem biosynthesis cluster protein A {ECO:0000303|PubMed:26213965};
GN   Name=penA {ECO:0000303|PubMed:26213965};
OS   Penicillium crustosum (Blue mold fungus).
OC   Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Eurotiomycetes;
OC   Eurotiomycetidae; Eurotiales; Aspergillaceae; Penicillium.
OX   NCBI_TaxID=36656;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA], IDENTIFICATION, FUNCTION, AND PATHWAY.
RC   STRAIN=PN2402;
RX   PubMed=26213965; DOI=10.3390/toxins7082701;
RA   Nicholson M.J., Eaton C.J., Starkel C., Tapper B.A., Cox M.P., Scott B.;
RT   "Molecular cloning and functional analysis of gene clusters for the
RT   biosynthesis of indole-diterpenes in Penicillium crustosum and P.
RT   janthinellum.";
RL   Toxins 7:2701-2722(2015).
CC   -!- FUNCTION: Part of the gene cluster that mediates the biosynthesis of
CC       the indole diterpenes penitrems (PubMed:26213965). The geranylgeranyl
CC       diphosphate (GGPP) synthase penG catalyzes the first step in penitrem
CC       biosynthesis via conversion of farnesyl pyrophosphate and isopentyl
CC       pyrophosphate into geranylgeranyl pyrophosphate (GGPP) (Probable).
CC       Condensation of indole-3-glycerol phosphate with GGPP by the prenyl
CC       transferase penC then forms 3-geranylgeranylindole (3-GGI) (Probable).
CC       Epoxidation by the FAD-dependent monooxygenase penM leads to a
CC       epoxidized-GGI that is substrate of the terpene cyclase penB for
CC       cyclization to yield paspaline (Probable). Paspaline is subsequently
CC       converted to 13-desoxypaxilline by the cytochrome P450 monooxygenase
CC       penP, the latter being then converted to paxilline by the cytochrome
CC       P450 monooxygenase penQ (PubMed:26213965). Paxilline is converted to
CC       beta-paxitriol via C-10 ketoreduction by the short-chain dehydrogenase
CC       PC-15 which can be monoprenylated at the C-20 by the indole diterpene
CC       prenyltransferase penD (Probable). A two-step elimination (acetylation
CC       and elimination) process performed by the O-acetyltransferase PC-16 and
CC       the P.simplicissimum ptmI-ortholog not yet identified in P.crustosum,
CC       leads to the production of the prenylated form of penijanthine
CC       (Probable). The FAD-linked oxidoreductase ptmO then converts the
CC       prenylated form of penijanthine into PC-M5 which is in turn transformed
CC       into PC-M4 by the aromatic dimethylallyltransferase PC-22 (Probable). A
CC       series of oxidation steps involving 4 cytochrome P450 monooxygenases
CC       (PC-21, PC-05, PC-23, PC-20) and a FAD-dependent monooxygenase (PC-14)
CC       are required for the transformation of PC-M4 to penitrems A and E.
CC       Synthesis of these final products is proposed to proceed via penitrems
CC       D and C (PC-21, PC-05, PC-14) and penitrems B and F (PC-21, PC-05, PC-
CC       14, PC-23) (Probable). {ECO:0000269|PubMed:26213965,
CC       ECO:0000305|PubMed:26213965}.
CC   -!- PATHWAY: Secondary metabolite biosynthesis.
CC       {ECO:0000305|PubMed:26213965}.
CC   -!- SUBCELLULAR LOCATION: Membrane {ECO:0000255}; Multi-pass membrane
CC       protein {ECO:0000255}.
CC   -!- SIMILARITY: Belongs to the membrane-bound ascI terpene cyclase family.
CC       {ECO:0000305}.
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DR   EMBL; KC963408; AGZ20193.1; -; Genomic_DNA.
DR   AlphaFoldDB; A0A0E3D8L0; -.
DR   SMR; A0A0E3D8L0; -.
DR   GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR   GO; GO:0016853; F:isomerase activity; IEA:UniProtKB-KW.
PE   3: Inferred from homology;
KW   Isomerase; Membrane; Transmembrane; Transmembrane helix.
FT   CHAIN           1..368
FT                   /note="Terpene cyclase penA"
FT                   /id="PRO_0000446541"
FT   TRANSMEM        10..30
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        81..101
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        118..138
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        192..212
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        233..253
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        334..354
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
SQ   SEQUENCE   368 AA;  40724 MW;  F56D99C0A94DED94 CRC64;
     MSHVVRPILI ILASVAIYTK YYLSFQNGFI DLLSTMGSQG SLAGLQDGLR SHYTGLDPLD
     KFLKACNVFF WPIFHGTSPA LSLYAIAFAG SMIPMWLILL MHTCVKSSIV EIVMINALTG
     LLVQGIGPGV MMCVLLAMRS TSMEEFAVTS IPAVSILGPN DLPLSLVVCY ILPLALSSLP
     APASISVPSK QLFIASWQGW PLYIALAVGI AHSLRYGYRR SRPQQLFRHA YAFALACSII
     SHVGLLLISF LSIYPKSPFL SLHSADLHPQ SLLVPRLPWQ EVKITSLESG VLRFLHWDYS
     ISSTGALLWC YDVYWEDRMR GKGWIAFFSL SSQLATMSLA FGPCSVALAL YWTALSKNLM
     KNEHVRKR